Since its original funding in 1975, this grant has been committed to the study of sensory mechanisms in the spinal cord. In recent years the research has focused on the identification of neuromediators released by nerve fibers that reach the spinal cord directly from the periphery. During the last years of support from this grant, research has also been undertaken to study the consequences of peripheral nerve injury on spinal cord. The plan for the next years follows these two main lines of investigation. To address the question of neurotransmitters released by primary afferents, the first project will: (l) test whether primary afferent terminals, both of myelinated and unmyelinated fibers, in the spinal cord are enriched with glutamate; 2) test whether aspartate is also enriched in these terminals; 3) explore the issue of presynaptic inhibition of these terminals. For this aim electron microscopic, double-staining, postembedding immunocytochemistry will be employed. This will be combined with the identification of primary afferent terminals by transport of tracers. Identification of the chemical mediators involved in the physiological transmission of sensory stimuli from the periphery is a prerequisite for the effective treatment of various sensory syndromes, including chronic pain. The second project will explore the hypothesis that peripheral nerve injury is signaled to the central nervous system (among other possible mechanisms) by the release of neuromediators whose function has yet to be elucidated (neuropeptides?). Preliminary evidence suggests this possibility, and also indicates that signaling of peripheral events may occur via release of agents that do not act at synapses, but at non- synaptic regions of the terminal's membrane. The release mechanism that will be explored by this second part of the research plan may represent a mode of intercellular communication involved in various post-lesion phenomena.